Abstract

OBJECTIVE
To explore the expression and significance of phosphatidylinositol-3 kinase (PI3K) in ovarian cancer, and the effect of combined PI3K inhibitor (LY294002) therapy with cisplatin on epithelial ovarian carcinoma, and to explore if there is a synergistic effect between the two therapies.
METHODS
The expression levels of PI3K p85 subunit proteins and mRNA were evaluated by western blot and RT-PCR in normal ovarian tissue (G1), ovarian benign tumor tissue (G2), ovarian borderline tumor tissue (G3) and ovarian cancer tissue (G4), and the relevant clinical pathological parameters were analyzed. SKOV3 cells were isolated and cultured by enzymolysis method. SKOV3 cells were treated with culture medium only, LY294002 (1, 10, 30, 50, 100 micromol/L), cisplatin (0.33, 1.25, 2.5, 5, 10 micromol/L), LY294002 (50 micromol/L) + cisplatin (10 micromol/L) for 2 days, respectively. The effect of LY294002 and cisplatin on the growth of SKOV3 cells was measured by methyl thiazolyl tetrazolium assay.
RESULTS
There was no positive expression of PI3K p85 subunit proteins in G1 and G2, while the expression was 2/6 in G3, and 85% (33/39) in G4. PI3K p85 subunit mRNA expression levels were 0.178 +/- 0.102 in G1, 0.643 +/- 0.112 in G2, 0.847 +/- 0.058 in G3, 1.689 +/- 0.423 in G4; there was a significant difference between G1, G2, G3 and G4 (P<0.01). There was no significant correlation between protein expression and age at surgery or clinico-pathological staging (P>0.05). Significant differences were noted between protein expression levels in G4 (III, IV) and G4 (I, II; P<0.05). There was a significant difference between expression levels in tissues of different differentiation degrees (P<0.05). LY294002 and cisplatin inhibited the growth of SKOV3 cell in a concentration-dependent manner. The inhibitory activity of LY294002 at the concentration of 50 micromol/L was (46.0 +/- 2.0)% after treatment for two days. The inhibitory activity of cisplatin at the concentration of 10 micromol/L was (44.4 +/- 3.2)% after treatment for two days. After treatment for two days, the inhibitory activity of LY294002 50 micromol/L + cisplatin 10 micromol/L was (57.1 +/- 4.1)%. The inhibition effect on SKOV3 cell growth of the combined treatment group was better than the LY294002 or cisplatin treated group (P<0.01).
CONCLUSIONS
PI3K p85 subunit is highly expressed and positively correlated with ovarian cancer. Different expression levels exist in tissues of late ovarian cancer, earlier ovarian cancer, borderline tumor, benign ovarian tumor and normal ovarian tissue. The changes in PI3K p85 subunit are correlated with tumor differentiation degree, but not pathologic typing. LY294002 combined with cisplatin can significantly enhance the killing efficiency in ovarian cancer cells.